芍藥屬（paeonia）是芍藥科（paeoniaceae）唯一屬，主要觀賞花卉為牡丹。英語和其他歐洲語言的牡丹和芍藥是同一個詞（paeony或peony）。此名來自古希臘神話阿波羅之子醫神阿斯克勒庇厄斯的門徒庇恩（Paeon），其醫術高明，先後治癒了戰神阿瑞斯、冥王哈迪斯，隨後得到眾神青睞，比如阿波羅之母黑暗女神勒託就賜了他一株奧林匹斯山的神聖藥草，這引起了阿斯克勒庇俄斯的嫉妒，準備幹掉庇恩，宙斯聽說以後，趕緊把庇恩變成了芍藥以免遭毒手。芍藥一般可以存活數年，牡丹可以存活30～60年，兩者均可入藥。清朝曾將牡丹定為國花。2019年7月15日，中國花卉協會發布《徵求牡丹為我國國花意見的通知》（中花協字【2019】16號）。2019年10月24日，《美國醫學會雜誌》腫瘤學分冊在線發表了以PEONY命名的亞洲乳腺癌雙靶新輔助治療研究簡報。
2012年和2016年英國《柳葉刀》腫瘤學分冊發表的NEOSPHERE國際多中心隨機非盲對照二期臨床研究短期和長期分析報告，已經證實了帕妥珠單抗＋曲妥珠單抗＋多西他賽新輔助治療早期或局部晚期HER2陽性乳腺癌術前患者的有效性、安全性和耐受性，與曲妥珠單抗＋多西他賽相比，病理完全緩解率顯著提高（45.8%比29.0%）。不過，該研究的亞洲患者比例僅佔22.78%。
2019年10月24日，《美國醫學會雜誌》腫瘤學分冊在線發表復旦大學附屬腫瘤醫院邵志敏和李俊傑、哈爾濱醫科大學附屬黑龍江省腫瘤醫院龐達、中國科學院大學附屬浙江省腫瘤醫院楊紅健、吉林大學白求恩第一醫院李薇、中山大學附屬腫瘤醫院王樹森、鄭州大學附屬河南省腫瘤醫院崔樹德、廣東省醫學科學院廣東省人民醫院廖寧、山東省醫學科學院山東省腫瘤醫院王永勝、福建醫科大學附屬協和醫院王川、馬偕紀念醫院張源清、中國醫藥大學附設醫院王惠暢、上海交通大學醫學院附屬瑞金醫院沈坤煒、解放軍總醫院第五醫學中心江澤飛、韓國亞洲大學醫學院姜錫潤、高麗大學九老醫院徐在弘、泰國宋卡王子大學醫院、羅氏全球藥品開發上海中心、美國基因泰克的PEONY研究簡報，比較了帕妥珠單抗或安慰劑＋曲妥珠單抗＋多西他賽新輔助治療亞洲早期或局部晚期HER2陽性乳腺癌術前患者的有效性、安全性和耐受性。
PEONY (A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate Pertuzumab in Combination With Docetaxel and Trastuzumab as Neoadjuvant Therapy, and Pertuzumab in Combination With Trastuzumab as Adjuvant Therapy After Surgery and Chemotherapy in Patients With Early-Stage or Locally Advanced HER2-Positive Breast Cancer): Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel (NCT02586025)
該亞洲多中心隨機雙盲安慰劑對照三期臨床研究於2016年3月14日～2017年3月13日從中國大陸和臺灣、韓國、泰國入組原發腫瘤大於2釐米的早期（T2-3、N0-1、M0）或局部晚期（T2-3、N2-3，M0；T4、任何N、M0）HER2陽性乳腺癌女性患者329例，按2∶1隨機分為兩組，術前每3周靜脈注射帕妥珠單抗（首次840毫克、隨後420毫克）或安慰劑、曲妥珠單抗（每公斤體重首次8毫克、隨後6毫克）、多西他賽（每平方米體表面積75毫克）共計12周；術後每3周靜脈注射氟尿嘧啶＋表柔比星＋環磷醯胺共計9周，隨後每3周靜脈注射帕妥珠單抗或安慰劑＋曲妥珠單抗共計39周，整個療程長達1年。
本文對截至2017年10月23日的數據進行分析：對意向治療患者進行主要終點分析，對實際治療患者進行不良事件分析。主要終點為獨立評審委員會評定的總體病理完全緩解率。按疾病分類和激素受體狀態進行分層，通過雙側分層卡方檢驗，對兩組患者進行比較。
結果，意向治療患者共計329例，平均年齡48.8±9.5歲，中國大陸＋臺灣患者比例佔88.75%；帕妥珠單抗組剔除1例不符合條件的患者，實際治療患者共計328例。
帕妥珠單抗組與安慰劑組相比：
因此，該研究結果表明，對於亞洲早期或局部晚期HER2陽性乳腺癌患者，帕妥珠單抗＋曲妥珠單抗＋多西他賽與安慰劑＋曲妥珠單抗＋多西他賽相比，術前新輔助治療的總體病理完全緩解率顯著較高。不良事件數據符合已知的帕妥珠單抗安全性，兩組患者大多數不良事件的發生率相似，除了帕妥珠單抗組≥3級中性粒細胞減少發生率和嚴重不良事件發生率稍高。該研究進一步擴充了帕妥珠單抗治療方案的獲益數據總量。
相關閱讀
JAMA Oncol. 2019 Oct 24. [Epub ahead of print]
Efficacy, Safety, and Tolerability of Pertuzumab, Trastuzumab, and Docetaxel for Patients With Early or Locally Advanced ERBB2-Positive Breast Cancer in Asia: The PEONY Phase 3 Randomized Clinical Trial.
Zhimin Shao, Da Pang, Hongjian Yang, Wei Li, Shusen Wang, Shude Cui, Ning Liao, Yongsheng Wang, Chuan Wang, Yuan-Ching Chang, Hweichung Wang, Seok Yun Kang, Jae Hong Seo, Kunwei Shen, Suphawat Laohawiriyakamol, Zefei Jiang, Junjie Li, Julian Zhou, Betsy Althaus, Yixiang Mao, Jennifer Eng-Wong.
Fudan University Shanghai Cancer Center, Shanghai, China; Harbin Medical University Cancer Hospital, Harbin, China; Zhejiang Cancer Hospital, Hangzhou, China; The First Hospital of Jilin University, Changchun, China; Sun Yat-sen University Cancer Center, Guangzhou, China; Henan Cancer Hospital, Zhengzhou, China; Guangdong General Hospital, Guangzhou, China; Shandong Cancer Hospital, Jinan, China; Fujian Medical University Union Hospital, Fuzhou, China; Mackay Memorial Hospital, Taipei City, Taiwan; China Medical University Hospital, Taichung City, Taiwan; Ajou University School of Medicine, Suwon, Korea; Korea University Guro Hospital, Seoul, Korea; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Songklanagarind Hospital, Songkhla, Thailand; The Affiliated Hospital of Military Medical Sciences (The 307th Hospital of Chinese People's Liberation Army), Beijing, China; Roche Product Development, Shanghai, China; Genentech, Inc, South San Francisco, California.
This phase 3 randomized clinical trial compares the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer.
QUESTION: Do Asian patients with ERBB2-positive early or locally advanced breast cancer benefit from the addition of pertuzumab to trastuzumab and docetaxel in the neoadjuvant setting, compared with placebo, trastuzumab, and docetaxel?
FINDINGS: In this randomized clinical trial of 329 women with early or locally advanced breast cancer, total pathologic complete response rates were 39.3% with pertuzumab and 21.8% with placebo, a significant difference. Safety data were generally comparable between groups.
MEANING: Pertuzumab, trastuzumab, and docetaxel significantly improved total pathologic complete response rate vs placebo, trastuzumab, and docetaxel in the neoadjuvant setting; this study adds to the totality of the data showing the benefit of the pertuzumab regimen.
IMPORTANCE: Prospective assessment of treatments known to benefit patients in global clinical trials in specific racial groups is essential.
OBJECTIVE: To compare the efficacy, safety, and tolerability of adding pertuzumab to trastuzumab and docetaxel vs placebo, trastuzumab, and docetaxel in Asian patients with ERBB2-positive early or locally advanced breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind, placebo-controlled phase 3 trial enrolled 329 women with ERBB2-positive early (T2-3, N0-1, M0) or locally advanced breast cancer (T2-3, N2 or N3, M0; T4, any N, M0) and primary tumor larger than 2 cm from March 14, 2016, to March 13, 2017. Analysis of the primary end point was performed on an intention-to-treat basis.
INTERVENTIONS: Before surgery, patients received 4 cycles of intravenous pertuzumab (840-mg loading dose and 420-mg maintenance doses), trastuzumab (8-mg/kg loading dose and 6-mg/kg maintenance doses), and docetaxel (75 mg/m2) or intravenous placebo, trastuzumab, and docetaxel every 3 weeks. After surgery, patients received 3 cycles of intravenous fluorouracil, epirubicin, and cyclophosphamide followed by 13 cycles of the same intravenous anti-ERBB2 therapy (pertuzumab and trastuzumab or placebo and trastuzumab) for up to 1 year.
MAIN OUTCOMES AND MEASURES: The primary end point was independent review committee-assessed total pathologic complete response rate. The 2-sided Cochran-Mantel-Haenszel test, stratified by disease category and hormone receptor status, was used to compare rates between treatment groups.
RESULTS: In total, 329 female patients were randomized (pertuzumab, 219; and placebo, 110; mean [SD] age, 48.8 [9.5] years). In the intention-to-treat population, total pathologic complete response rates were 39.3% (86 of 219) in the pertuzumab group and 21.8% (24 of 110) in the placebo group (difference, 17.5% [95% CI, 6.9%-28.0%]; P = .001). Of the most common grade 3 or higher adverse events, there was a higher incidence of neutropenia in the pertuzumab group (83 of 218 [38.1%] vs 36 of 110 [32.7%]). Serious adverse events were reported in 10.1% of patients (22 of 218) in the pertuzumab group and 8.2% of patients (9 of 110) in the placebo group.
CONCLUSIONS AND RELEVANCE: Treatment with pertuzumab, trastuzumab, and docetaxel resulted in a statistically significant improvement in the total pathologic complete response rate vs placebo, trastuzumab, and docetaxel for the neoadjuvant treatment of ERBB2-positive early or locally advanced breast cancer in Asian patients. Safety data were in line with the known pertuzumab safety profile and generally comparable between treatment groups. The PEONY trial adds to the totality of data showing the benefit of the pertuzumab regimen.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02586025
DOI: 10.1001/jamaoncol.2019.3692